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Case: 16-2116 Document: 25 Page: 1 Filed: 11/23/2016

2016-2116

UNITED STATES COURT OF APPEALS


FOR THE FEDERAL CIRCUIT

ABT HOLDING COMPANY

and

REGENTS OF THE UNIVERSITY OF MINNESOTA,


Appellants,

v.
GARNET BIOTHERAPEUTICS, INC.,
Appellee.

Appeal from the United States Patent and Trademark Office,


Patent Trial and Appeal Board in Interference No. 105,953.

CORRECTED RESPONSE BRIEF OF APPELLEE


GARNET BIOTHERAPEUTICS, INC.
_____________________________________________________________

Cynthia M. Bouchez Matthew J. Dowd


Medler Ferro Woodhouse & Dowd PLLC
Mills PLLC 1717 Pennsylvania Avenue, NW
8201 Greensboro Drive Suite 1025
Suite 1060 Washington, D.C. 20006
McLean, VA 22102 (202) 573-3853
cbouchez@medlerferro.com mjdowd@dowdpllc.com

Counsel for Appellee


Garnet BioTherapeutics, Inc.
Case: 16-2116 Document: 25 Page: 2 Filed: 11/23/2016

CERTIFICATE OF INTEREST

Counsel for Appellee Garnet BioTherapeutics, Inc. certifies the


following:

1. The full name of every party or amicus represented by me is:

Garnet BioTherapeutics, Inc.

2. The name of the real party in interest (if the party named in the
caption is not the real party in interest) represented by me is:

Not Applicable

3. All parent corporations and any publicly held companies that own
10 percent or more of the stock of the party or amicus curiae
represented by me are:

Not Applicable

4. The names of all law firms and the partners or associates that
appeared for the party or amicus now represented by me in the trial
court or agency or are expected to appear in this court are:

Matthew J. Dowd, Dowd PLLC, 1717 Pennsylvania Avenue,


NW, Suite 1025, Washington, D.C. 20006;
Cynthia M. Bouchez, Medler Ferro Woodhouse & Mills PLLC,
8201 Greensboro Drive, Suite 1060, McLean, VA 22102

Date: November 22, 2016 /s/ Matthew J. Dowd


Signature of counsel

Matthew J. Dowd
Printed name of counsel
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TABLE OF CONTENTS
Page

STATEMENT OF RELATED CASES ....................................................... 1

STATEMENT OF THE ISSUES ................................................................ 1

STATEMENT OF THE CASE AND FACTUAL BACKGROUND ........... 1

I. Procedural Background ..................................................................... 1

II. Factual Background .......................................................................... 3

A. The Basics of Stem Cell Technology ........................................ 4

B. Multipotent Progenitor Cells Are Characterized by


Particular Physical Features and the Methods Used to
Isolate and Culture the Cells ................................................... 7

C. The Isolation and Culturing of Multipotent Progenitor


Cells are Difficult and Depend on the Tissue Source
and the Methods Used............................................................ 10

D. Dr. Verfaille and Colleagues Report on the Isolation of


a Multipotent Adult Progenitor Cell (“MAPC”), But
They Later Retract One Publication Due To Falsified
Data ......................................................................................... 15

E. Notwithstanding the Falsified Data, Verfaille and Her


Fellow Furcht Inventors Sought Broad Claims
Covering Their MAPCs .......................................................... 18

F. Ho and His Colleagues File Patent Applications


Directed to a Different Stem Cell Population Co-
Expressing CD49c and CD90 ................................................. 20

G. After Repeated Attempts by Furcht, the Board


Declares an Interference Between Ho and Furcht ............... 21

H. The Board Rules in Favor of Ho on the Motions of No


Interference-in-Fact and Lack of Written Description ......... 23

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SUMMARY OF THE ARGUMENT ......................................................... 28

ARGUMENT ............................................................................................. 30

I. Standard Of Review......................................................................... 30

II. The Board Did Not Adopt Or Rely On An “Improper”


Definition Of The Level Of Ordinary Skill In The Art .................. 31

III. The Board Did Not Err In Crediting The Testimony of Ho’s
Experts Over Furcht’s Experts ....................................................... 34

IV. The Board Correctly Found That Stem Cell Technology Was
Unpredictable in 1999-2000 ............................................................ 39

V. Substantial Evidence Supports The Board’s Finding That


The Furcht ‘037 Claims Are Not “Inherently” Described In
The Furcht Specification ................................................................. 43

A. Legal Standard for the Written Description


Requirement ........................................................................... 44

B. The Board Correctly Identified Significant Differences


Between the Methods Used in the Deans Experiments
and the Method Used in the Furcht Application .................. 46

C. The Board Did Not Misconstrue the Definition of “Co-


Express” .................................................................................. 53

VI. Substantial Evidence Supports The Board’s Finding That


The Furcht ‘118 Claims Do Not Satisfy The Written
Description Requirement ................................................................ 61

A. The Furcht Disclosure Does Not Demonstrate


Possession of the Broadly Claimed Cells .............................. 62

B. This Court’s Precedent Supports the Board’s Decision ........ 64

C. The Court Did Not Err Concerning the “Two Facts”


Identified by ABT ................................................................... 67

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VII. ABT’s Challenge To The Board’s Decision On The Furcht


‘256 Claims Repeats Its Factual Challenges And Should Be
Rejected For The Same Reasons ..................................................... 69

VIII. The Board Correctly Held That No Interference-In-Fact


Existed Between Any Furcht Claim And Any Ho Claim ............... 71

A. Legal Standard ....................................................................... 71

B. ABT’s Argument is Entirely Based on the Same


Arguments Concerning Written Description ........................ 72

IX. If The Court Remands, The Board Should Rule That The
Furcht Claims Are Not Enabled ..................................................... 73

X. Conclusion ........................................................................................ 73

CERTIFICATE OF COMPLIANCE

CERTIFICATE OF SERVICE

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TABLE OF AUTHORITIES

Page(s)

Cases

AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc.,


759 F.3d 1285 (Fed. Cir. 2014) ...................................................... 66, 67

Agilent Technologies, Inc. v. Affymetrix, Inc.,


567 F.3d 1366 (Fed. Cir. 2009) ...................................................... 53, 58

Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.,


598 F.3d 1336 (Fed. Cir. 2010) (en banc) ...................................... 64, 66

Ashland Oil, Inc. v. Delta Resins & Refractories, Inc.,


776 F.2d 281 (Fed. Cir. 1985) .............................................................. 39

Bamberg v. Dalvey,
815 F.3d 793 (Fed. Cir. 2016) .............................................................. 31

Biogen Idec, Inc. v. GlaxoSmithKline LLC,


713 F.3d 1090 (Fed. Cir. 2013) ............................................................ 54

Biogen MA, Inc. v. Japanese Foundation for Cancer Research,


785 F.3d 648 (Fed. Cir. 2015) ................................................................ 3

Capon v. Eshhar,
418 F.3d 1349 (Fed. Cir. 2005) ............................................................ 65

Carnegie Mellon University v. Hoffmann-La Roche, Inc.,


541 F.3d 1115 (Fed. Cir. 2008) ................................................ 44, 65, 66

Chen v. Bouchard,
347 F.3d 1299 (Fed. Cir. 2003) ............................................................ 31

Consolidated Edison Co. v. NLRB,


305 U.S. 197 (1938) .............................................................................. 31

Consolo v. Federal Maritime Commission,


383 U.S. 607 (1966) ........................................................................ 31, 40

-v-
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DeGeorge v. Bernier,
768 F.2d 1318 (Fed. Cir. 1985) ............................................................ 43

Dystar Textilfarben GmbH v. C.H. Patrick Co.,


464 F.3d 1356 (Fed. Cir. 2006) ............................................................ 32

Eli Lilly v. Board of Regents of the Univeristy of Washington,


334 F.3d 1264 (Fed. Cir. 2003) ............................................................ 72

Enzo Biochem, Inc. v. Calgene, Inc.,


188 F.3d 1362 (Fed. Cir. 1999) ............................................................ 42

Enzo Biochem, Inc. v. Gen-Probe Inc.,


323 F.3d 956 (Fed. Cir. 2002) .............................................................. 45

Fenner Investments, Ltd. v. Cellco Partnership,


778 F.3d 1320 (Fed. Cir. 2015) ............................................................ 54

Graham v John Deere Co.,


383 U.S. 1 (1966) .................................................................................. 32

Harari v. Lee,
656 F.3d 1331 (Fed. Cir. 2011) ...................................................... 31, 53

Hyatt v. Boone,
146 F.3d 1348 (Fed. Cir. 1998) ............................................................ 43

In re Alton,
76 F.3d 1168 (Fed. Cir. 1996) .............................................................. 45

In re Fisher,
427 F.2d 833 (C.C.P.A. 1970) ............................................................... 65

In re Gartside,
203 F.3d 1305 (Fed. Cir. 2000) ...................................................... 30, 32

In re Jolley,
308 F.3d 1317 (Fed. Cir. 2002) ............................................................ 31

In re Spina,
975 F.2d 854 (Fed. Cir. 1992) ........................................................ 53, 58

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Martin v. Mayer,
823 F.2d 500 (Fed. Cir. 1987) .............................................................. 43

Medichem, S.A. v. Rolabo, S.L.,


437 F3d 1157 (Fed. Cir. 2006) ............................................................. 72

Medichem, S.A. v. Rolabo, S.L.,


353 F.3d 928 (Fed. Cir. 2003) .............................................................. 72

Microsoft Corp. v. Proxyconn, Inc.,


789 F.3d 1292 (Fed. Cir. 2015) ............................................................ 54

Newell Cos., Inc. v. Kenney Manufacturing Co.,


864 F.2d 757 (Fed. Cir. 1988) .............................................................. 35

O’Reilly v. Morse,
56 U.S. (15 How.) 62 (1853) ................................................................. 44

Regents of the University of California v. Eli Lilly & Co.,


119 F.3d 1559 (Fed. Cir. 1997) ............................................................ 67

Sage Products, Inc. v. Devon Industries, Inc.,


126 F.3d 1420 (Fed. Cir. 1997) ............................................................ 38

University of Rochester v. G.D. Searle & Co.,


358 F.3d 916 (Fed. Cir. 2004) .............................................................. 45

Velander v. Garner,
348 F. 3d 1359 (Fed. Cir. 2003) ..................................................... 39, 47

Statutes

28 U.S.C. § 1631 .......................................................................................... 3

35 U.S.C. § 112 .................................................................................. passim

28 U.S.C. § 146 ............................................................................................ 3

Regulations

37 C.F.R. § 41.203(a) ................................................................................. 72

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Other Authorities

The Guidelines for Examination of Patent Applications under the 35


U.S.C. § 112, ¶ 1, “Written Description” Requirement,
66 Fed. Reg. 1099 (Jan. 5, 2001) .......................................................... 65

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STATEMENT OF RELATED CASES

Pursuant to Fed. Cir. R. 47.5, there are no related appeals, and

counsel is unaware of any cases that may be affected by this appeal.

STATEMENT OF THE ISSUES

1. Whether substantial evidence supports the Board’s

determination that the involved Furcht claims are not patentable

because the Furcht claims did not satisfy the written description

requirement of 35 U.S.C. § 112.

2. Whether the Board correctly decided that there was no

interference-in-fact when substantial evidence supports (a) the finding

that at least one Furcht claim does not anticipate at least one Ho claim

and (b) the legal conclusion that at least one Furcht claim does not

render at least one Ho claim obvious.

STATEMENT OF THE CASE


AND FACTUAL BACKGROUND

I. Procedural Background

This is an appeal from the final decision of the Patent Trial and

Appeal Board (“Board”), dated September 26, 2014, between senior

party Furcht and junior party Ho. Appx1-64. The Board’s final

judgment was entered the same day. Appx47-50.

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The Board decided two of the three motions filed by Ho.1 First, Ho

filed a motion asserting that no interference-in-fact existed between any

Furcht claim and any Ho claim. Appx866-897. Second, Ho filed a

motion that all of Furcht’s involved claims were not patentable because

they failed to satisfy the written description and enablement

requirements of 35 U.S.C. § 112. Appx719-754. Furcht opposed the

motions but did not file any motions of its own. Appx907-988. Ho filed

replies. Appx1240-1342. Oral argument on the motions occurred on

July 30, 2014. Appx1387-1425.

On September 26, 2014, the Board ruled in favor of Ho on two

motions, finding that the Furcht claims were not supported by the

written description and that there was no interference-in-fact.

Appx1-50. The Board entered judgment against senior party Furcht

and ordered that the involved claims of the Furcht patents and

applications be cancelled or refused. Appx1-50. The Board did not rule

on whether the Furcht claims were adequately enabled under § 112.

Appx45.

1The Board dismissed as moot Ho Motion 3 seeking an order denying


priority benefit of the two Furcht provisional applications. Appx7.

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After the final judgment, the senior party, ABT Holding Company

and Regents of the University of Minnesota (collectively “ABT”) filed a

civil action, pursuant to 35 U.S.C. § 146, in the United States District

Court for the District of Delaware. Appx1448. While that action was

pending, this Court decided Biogen MA, Inc. v. Japanese Foundation for

Cancer Research, 785 F.3d 648 (Fed. Cir. 2015), cert. denied, 136 S. Ct.

1450 (2016), which held that a civil action under 35 U.S.C. § 146 is not

available for an interference proceeding declared after September 15,

2012. After the Supreme Court declined to review Biogen, the trial

court granted Garnet BioTherapeutics, Inc.’s motion to dismiss. The

trial court transferred the case to this Court pursuant to 28 U.S.C.

§ 1631.

II. Factual Background

Garnet provides a concise counterstatement of the facts. ABT’s

opening Statement of the Facts contains assertions lacking citation to

the record and non-factual assertions that constitute attorney

argument. See, e.g., Appellant Br. 13 (“The Board erred in finding for

Ho.”).

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A. The Basics of Stem Cell Technology

The present appeal relates to what are commonly referred to as

“stem cells.” Appx9-12; Appx2032-2977; Appx3493; Appx3602-3606.

The quintessential stem cell is the “embryonic stem cell,” which can

differentiate into every type of cell in the body, such as a skin cell,

muscle cell, or nerve cell, and in particular, cells of the three different

basic germ layers: ectoderm, endoderm, and mesoderm. Appx2970-

2972. Embryonic stem cells are isolated from an embryo during the

first few days of development. Appx3493. “As stem cells within a

developing human embryo differentiate in vivo, their capacity to

diversify generally becomes more limited and their ability to generate

many differentiated cell types generally becomes more restricted.”

Appx3493-3494.

Even in adulthood, the body contains adult “stem” cells of various

degrees of “pluripotency” or “multipotency.”2 Appx3402; Appx3605.

While the terminology used to describe stem cells is often imprecise,

under one definition, “[p]luripotent stems cells are capable to

differentiate into the three somatic germ layers that comprise an

2 Adult stem cells can also be referred to as adult progenitor cells.

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organism: mesoderm (muscle, bone, etc.), ectoderm (neurons, skin, etc.),

and endoderm (hepatocytes, pancreatic beta cells, etc.), whereas

multipotent cells can differentiate only into cells of one tissue or germ

layer.” Appx3402; see also Appx3605; Appx3644-3645.

For example, a multipotent blood stem cell, called a hematopoietic

stem cell, can differentiate into various blood cells, such as red blood

cells and white blood cells, but not into brain cells, bone cells, or other

types of cells. Appx3022-3027; Appx3037-3043. Similarly,

mesenchymal stem cells (“MSCs”) are isolated from bone marrow and

can differentiate into bone cells (osteoblasts), cartilage cells

(chondrocytes), muscles cells (myocytes), and fat cells (adipocytes).

Appx1588; Appx2911-2922; Appx3015-3021.

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Appx3016.

The various adult stem cells generally exist in the body in a

tissue-specific manner. In other words, an adult stem cell, such as a

mesenchymal stem cell (“MSC”), can be isolated from the bone marrow

and can differentiate into muscle cells but cannot differentiate into

brain or skin cells. Appx3022-3027; Appx3037-3107; Appx3274-3284.

Stem cells and multipotent progenitor cells have enormous

potential for scientific and medical uses. Appx108; Appx1549-1553;

Appx3028-3036. That greatest potential resides with embryonic stem

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cells because they can differentiate into any type of adult cell.

Appx3492-3496.

The use of embryonic stem cells presents thorny ethical issues,

however. Appx2979-2988. In August 2001, President Bush addressed

the nation and restricted funding to established embryonic stem cell

lines. Appx3487-3489. That development increased the need for an

alternative to embryonic stem cells, and one alternative sought was an

adult cell capable of differentiating into multiple cell lines. In the years

preceding the President’s decision, researchers had been advancing

their efforts to identify the so-called “Holy Grail” of stem cells: non-

embryonic, or adult, stems cells, i.e., adult cells that had the same

differentiating ability as embryonic stem cells. Appx2945-2947.

B. Multipotent Progenitor Cells Are Characterized by


Particular Physical Features and the Methods Used to
Isolate and Culture the Cells

Multipotent stem cells are not characterized simply by observing

the cell features under a microscope, unlike other cells, such as muscle

or skin cells. Appx3016. Instead, multipotent progenitor cells are

characterized based on certain phenotypic characteristics, the methods

used to prepare the stem cell cultures, and the tissue source of the cells.

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One important phenotypic characteristic is the identity of the

cellular proteins expressed by the particular cell population. Appx1528-

1529; Appx1603-1613; Appx3085. As Furcht points out in its opening

brief, the type of “stem cell” is reflected in the cell’s gene expression,

which in turn is often but not always reflected in the differential

expression of various proteins on a cell. Appellant Br. 6; see also

Appx1603-1613. The marker proteins (or epitopes) are designated

using various monikers such as CD34, CD44, CF45, HLA Class I,

CD49c, Muc18, and others. E.g., Appx214; Appx3085. Two marker

proteins of particular importance in this case are CD49c and CD90.

Appx52-56; Appx2369-2382.

While the precise roles of the various protein markers are not

always fully understood, Appx2921, it is understood that individual cell

populations having different protein expression profiles are not

identical cell populations. Appx2416-2438. For example, a cell

population in which 90 percent of cells express CD49c is different than

a cell population in which only 10 percent express CD49c. Appx2416-

2438.

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A stem cell population is also characterized by the doubling rate of

the population. Appx2004-2005; Appx2423-2433. The doubling rate of

a cell population describes the time necessary for the population to

double in number, or size, and is expressed in hours. Appx1972-1981;

Appx2416-2438. The lower the doubling rate, the faster the particular

stem cells grow and divide. Appx2416-2438. The doubling rate is

important because stem cell populations that have different doubling

rates are likely expressing different proteins and are likely at different

stages of differentiation. Appx2911 (“[A]s cultures of the cells are

expanded under standard conditions, they lose their proliferative

capacity and their potential to differentiate into lineages such as

adipocytes and chrondocytes.”); Appx1973 (Dr. Phinney explaining that

“modifying the doubling rate of cells” can alter “the properties of the

cells themselves”).

In addition to protein expression profiles and doubling rate, adult

stem cells are often described according to the tissue source of the cells

and the methods used to isolate and culture the cells. As explained

below, the tissue source and the methods used will alter the identity of

the isolated and cultured stem cell population.

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C. The Isolation and Culturing of Multipotent Progenitor Cells


are Difficult and Depend on the Tissue Source and the
Methods Used

Around 1999 to 2000, multipotent stem, or progenitor, cells were

notoriously difficult to characterize, isolate, and maintain in cell

culture. Appx2921 (noting “[t]he difficulties in expanding human MSCs

in culture are compounded by the fact that there is no consensus as to

the characteristic surface epitopes that can be used to identify the

cells”); Appx4030 (Dr. Deans agreeing with previous statement);

Appx2947-2948; Appx3077-3091.

The identity of the isolated cell population depends on the

particular conditions, protocols, and equipment used. Appx1984;

Appx3091 (“Basal nutrients, cell density, spatial organization and

mechanical forces, as well as growth factors and cytokines, appear to

have profound influences on differentiation of hMSCs.”); Appx3277;

Appx3607-3617; Appx4043. Indeed, “the methods used to isolate cells

reflect unique properties of the cell’s biology.” Appx1984; see also

Appx3391 (“Differences in the properties of MSCs also depend on the

site of tissue harvest, phenotypic and genotypic characteristics of the

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donor and the isolation, and storage and expansions methods used.”);

Appx3274-3284.

Relevant parameters affecting the stem cell population include:

(1) oxygen content; (2) the cell culture medium; (3) the steps used to

process the cell tissue, including immunodepletion and centrifugation

step; (4) the type of vessel used to culture the cells; (5) cell density; and

(6) the tissue source of the cells. See Appx3936; Appx3607-3617.

The first important parameter is the oxygen content. Under

normal atmospheric conditions, oxygen is approximately 21% of the air.

Appx2422-2423; Appx2437. In contrast, stem cells in their native

environment may experience much lower levels of oxygen, such as 5%

oxygen. Appx1664. The difference in oxygen content is significant

because prolonged exposure to atmospheric oxygen can promote cell

damage, negatively affect growth and survival, and influence the

identity of the stem cell population that is isolated and cultured.

Appx1675-1677; Appx2437; Appx2926-2939. If a research publication is

silent on oxygen content, then the default condition is atmospheric

oxygen, or normoxia (21%), as opposed to 5% oxygen (“hypoxia”).

Appx4028.

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The cell culture medium also affects the identity of the stem cell

population. Appx1675-1677; Appx2422-2423; Appx3391. When stem

cells are isolated and cultured outside the body, they are grown in a cell

culture medium that supplies the necessary nutrients and growth

factors. Appx2437; Appx2883-2910; Appx2925 (discussing growth

factors); Appx3123. The composition of the cell culture medium affects

the fate of the stem cells, similar to when stem cells develop in the

human body. Appx2925. In other words, stem cells grown in one

medium or exposed to one environment may become different than cells

grown in or exposed to a different medium or environment. Appx3607-

3617.

A third factor affecting the stem cell population is the method

used to harvest and process the tissue culture before isolating and

expanding the stem cells. Appx17-18; Appx2070-2073; Appx2422-2423;

Appx2369-2382. When bone marrow is used as a source for potential

stem cells, the biological material consists primarily of red blood cells,

not stem cells. Appx2435-2436; Appx3607. Processing steps, such as

Ficoll-Paque density gradient or ammonium chloride lysis, are used to

remove red blood cells and other unwanted material. Appx18;

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Appx2070-2075. Immunodepletion can also remove cells of certain

known phenotypes. Appx18; Appx2960-2961. For instance, cells

expressing a specific protein marker, such as CD45, can be selectively

removed from the extract. Appx2960. These various steps are not

always used, and they lead to different results with different stem cell

populations. Appx18; Appx2070-2075; Appx2434-2436.

Fifth, the type of vessel in which stem cells are cultured can affect

the identity of the stem cell population obtained. Appx2422-2423. Two

common vessels used to isolate and culture stem cells are (1) the 96-well

plate and (2) the tissue culture flask. Appx2416. The two differ in

shape, size and surface area, which affect the type of cells grown and

isolated. Appx2416. Tissue culture flasks are generally used to grow a

large number of cells. Appx2416. The 96-well plate, in contrast, is

typically used to isolate a smaller number of specific cell

subpopulations. Appx2416.

A sixth factor affecting the stem cell culture is the cell culture

density. Appx4326. Cell culture density refers to the number of cells

that are initially added to a culture vessel with a defined surface area,

which determines whether the cells are densely packed or spread apart.

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This parameter is very cell-type specific, as some cells thrive when they

are in close proximity to other cells, while others thrive with more

space. Cells grown at a density other than what is recommended can

alter their phenotype. Appx4318-4323 (discussing Appx3402-3417). It

is “common knowledge” that cells grown at different cell culture

densities will develop into different cell populations. Appx4116. This

occurs because stem cells are affected by proximity to other cells in

culture, and the secretion of factors by the cell population as a whole.

For example, one method for triggering multipotent cells to differentiate

and become another phenotype is to culture them at a much higher

density than used for growing or expanding them. Appx1554-1559.

Finally, the source of the tissue affects the types of stem cells

obtained. Appx2963; Appx3121-3139; Appx3141-3144. For example,

mesenchymal stem cells (MSCs) are generally obtained from bone

marrow but not from neuronal tissue. Appx3391 (“Difference in the

properties of MSCs also depend on the site of tissue harvest . . . .”).

In sum, a range of factors materially affect the isolation and

culturing of stem cells. Appx2941-2968. For this reason, stem cell

scientists describe stem cell populations in terms of both certain

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physical features, such as protein markers and doubling rates, and the

conditions used to isolate and culture the cells. Appx3085.

D. Dr. Verfaille and Colleagues Report on the Isolation of a


Multipotent Adult Progenitor Cell (“MAPC”), But They Later
Retract One Publication Due To Falsified Data

Prior to 2002, adult stem (or progenitor) cells were understood to

have only limited ability to grow in culture and differentiate.

Appx2946. No one had identified an adult progenitor cell (or adult stem

cell) that could be grown and differentiated into cells of each of the

three germ layers. Appx2946 (Dr. Phinney describing the “Holy Grail”

of stem cell technology).

In 2002, Dr. Catherine Verfaille and her colleagues3 at the

University of Minnesota published a paper in Nature describing what

they termed “multipotent adult progenitor cells,” or “MAPCs” for short.4

Appx1644-1652. The Nature paper was among other Verfaille

publications, including reports in Blood and Experimental Hematology,

3Catherine Verfaille is one of the named inventors of the involved


Furcht patents and applications. Appx191.
4 MAPCs are also referred to as “multipotent adult stem cells,” or
“MASCs.” Appx4096-4097. Note that a MASC (or MAPC) is not the
same as a MSC (mesenchymal stem cell).

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detailing their work on MAPCs. Appx1635-1643; Appx1653-1663;

Appx3206-3212.

Verfaille reported specific conditions for isolating the MAPCs.

Appx1635-1643. Verfaille also characterized the cells based on the

protein expression, such as specifying CD45 negative, but did not

identify CD49c or CD90 as potential protein markers. Appx1635-1643.

Verfaille’s other publications did not identify the MAPCs as co-

expressing greater than 91% of both CD49c and CD90. See Appx1635-

1663.

Not long after Verfaille’s publications, questions arose about the

accuracy and reproducibility of Verfaille’s research on MAPCs.

Appx1620-1634. Other scientists were having significant difficulty

reproducing the Verfaille’s research results. E.g., Appx1623 (“Everyone

can agree on one thing about Catherine Verfaille’s stem cells, known as

MAPCs: they are fiendishly difficult to work with.”); Appx3359

(observing that MAPCs “have proven difficult to isolate and culture”).

In addition to the lack of reproducibility, it was subsequently

learned that several figures and data in the publications had been

falsified or misrepresented. Appx1620-1629; Appx1997-1998;

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Appx2412-2415; Appx2535-2540; Appx2955-2957; Appx3213-3229;

Appx3470-3472. As a consequence, the Nature paper was “corrected,”

and the Blood paper was retracted—a “significant event” for a scientist.

Appx1626; Appx3212; Appx4252.

Years later, Verfaille and her colleagues published additional

research that described different methods and conditions for isolating

the MAPCs. Appx3340-3365; Appx3418-3446. In one publication,

Verfaille explained that, “[s]ince 2003, culture conditions under which

rodent MAPCs are isolated have changed, including isolation and

maintenance at 5% oxygen, use of a different serum and maintenance at

higher cell densities for the first 4 weeks in culture, compared with the

previously described MAPCs.” Appx3341. In another article, Verfaille

reported using “low oxygen (O2) conditions,” different from their original

method. Appx3349 (“Since the initial description of MAPCs, we

improved MAPC isolation and expansion conditions.”). In 2001,

Verfaille further explained:

Major factors that play a role in successful maintenance of


MAPC include cell density, CO2 concentration and pH of the
medium, lot of fetal calf serum that is used, and even the
type of culture plastic that is used. Control of cell density
appears to be species specific . . . . The reason why MAPC

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tend to differentiate to the default MSC lineage when


maintained at higher densities is not known.

Appx3788.

While the falsification of data was certainly extraordinary, the

events associated with Verfaille’s disclosure and subsequent

modification of the procedures were representative of the general

unpredictability in the field at the time. Appx2001-2002; Appx2947-

2948; Appx2955-2957; Appx4030. Scientists were “eager to isolate a

phenotypically well-defined cell population with broad plasticity, but

there were no standard protocols, and no guidance existing regarding

how to obtain this goal.” Appx2948. The data-falsification incident

involving Verfaille’s work contributed to the substantial

unpredictability in the field. Appx4348. A 2007 report concluded that

“[t]he discovery of more duplicated data is again casting a shadow over

‘versatile’ adult stem cells.” Appx1622.

E. Notwithstanding the Falsified Data, Verfaille and Her


Fellow Furcht Inventors Sought Broad Claims Covering
Their MAPCs

Notwithstanding the reproducibility issues and data falsification,

Verfaille and colleagues filed several patent applications directed to

their MAPCs. Appx191-447. Two applications eventually issued as the

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Furcht ‘037 and ‘118 patents. Appx191-244; Appx393-447. The Furcht

specification provides a single example of isolating and culturing the

MAPCs. Appx220-221; Appx2948-2963. The Furcht method uses a cell

culture medium that requires supplemental growth factors for

maintaining proliferation of the stem cells derived from bone marrow.

Appx220, col. 17, table1. The Furcht specification further describes a

single method for isolating the claimed cells under standard, i.e.,

atmospheric, oxygen conditions. Appx2948-2955; Appx2958-2963.

“Standard conditions,” as explained above, means that the oxygen

content was approximately 21% (i.e., normoxia). Appx4028; Appx4109.

The Furcht specification also identifies the MAPCs according to

typical characteristics. The Furcht cells, after 10-12 cell doublings,

“stained positive with antibodies against CD10, CD13, CD49b, CDw90,

and Flk1.” Appx2953; Appx214, col.5, ll.60-67. Furcht also specified

that the cell population “has a doubling rate of about 36 hours.”

Appx243. Furcht’s cell population grows poorly and dies when seeded

at less than 500 cells/cm2. Appx219, col.15, ll.58-59.

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F. Ho and His Colleagues File Patent Applications Directed to a


Different Stem Cell Population Co-Expressing CD49c and
CD90

Around the same time the Furcht patent family was filed, Tony

Ho and his colleagues at Neuronyx, Inc., later renamed Garnet

BioTherapeutics, Inc., filed applications (the ‘244 and ‘685 applications)

directed to a different adult stem cell population isolated from bone

marrow. Appx51-190. The stem cell populations described and claimed

in the Ho applications co-express greater than 91% CD49c and CD90.

Appx88-101.

The Ho applications provided detailed examples of how the

claimed cells are isolated and cultured. Appx75-88; Appx144-165. The

cells are described as being (a) negative for surface marker CD10, and

(b) positive for surface markers CD44, HLA-class 1 and beta

2-microglobulin. Appx2541-2573. Ho’s cells are cultured at 30 cells/cm2

and thrive. Appx77-78; Appx2437.

Unlike the Furcht specification, the Ho applications describe cells

that are grown without the use of supplemental growth factors.

Appx2422-2423. Also in contrast to the Furcht specification, the

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method for growing the Ho cells uses 5% oxygen, whereas Furcht uses

21% oxygen. Appx2422-2423; Appx2437.

G. After Repeated Attempts by Furcht, the Board Declares an


Interference Between Ho and Furcht

Although the specifications and the claims of Ho’s applications

differed from Furcht’s applications and claims, Furcht repeatedly

attempted to initiate an interference between the parties. Appx2593-

2605; Appx2660-2661; Appx3222-3229. For instance, after Ho paid the

‘244 application’s issue fee in February 2005, Furcht amended its claims

in the application that later issued as the ‘037 patent to include the new

limitation that the cells co-express CD49c and CD90, even though the

limitation is not described in Furcht’s specification. Appx2423-2437.

Simultaneously, Furcht requested an interference with Ho’s ’244

application. Appx2593-2605. The PTO declined to declare the

interference and instead allowed the ‘037 patent to issue, continuing

examination of Ho’s ‘244 application. Appx2662-2674.

Ho’s ‘244 application subsequently overcame anticipation and

obviousness rejections based on Furcht’s ‘037 patent. Appx2606-2661.

The examiner ultimately concluded that the claimed CD49c/CD90 stem

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cell population in Ho’s application was not anticipated or obvious in

view of Furcht’s ‘037 patent. Appx2606-2661.

Ho appealed to the Board separate rejections in the ’244

application (along with rejections in Ho’s ‘685 application). Appx2606-

2661. The Board reversed the rejections, the claims were soon in

condition for allowance, but the examiner withheld the issuance after

communications from Furcht’s representatives. Appx2660-2661. A

notice of allowance subsequently issued in each of Ho’s applications.

Appx2662-2674; see also Appx2587-2592.

Before issuance, however, Furcht filed a notice of interfering

subject matter in its ‘256 application. Appx2593-2605. Along with each

interference request, Furcht included a declaration from Robert J.

Deans. Appx2459-2496 (collectively “the Deans Declarations”). The

Deans Declarations described two sets of experiments (“the Deans

Experiments”) which purported to demonstrate that the stem cell

population made according to the single method in the Furcht

specification is the same as the cell stem population claimed in Ho’s

applications. Appx2459-2496. Although Dr. Deans (or his colleagues)

had made stem cells according to the Furcht method, the Deans

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Declarations do not include those results. Appx2459-2496; Appx 4116-

4117. Instead, the Deans Declaration used different methods.

Appx2959-2961. Dr. Deans later contended that “[i]t was not necessary

or logical to” include results based on the Furcht method, even though

the purpose of the Deans Declarations was to prove that the Furcht

cells were the same as the Ho cells. Appx 4116-4117.

In response to the Deans Declarations, Ho filed a declaration (“the

Kopen Declaration”) from Dr. Gene Kopen, one of the inventors of the

Ho applications. Appx2541-2573. Dr. Kopen provided a detailed

explanation of why the cells in the ‘244 application are not the same as

the cells in the Furcht ‘037 patent. Appx2543-2564. After Furcht’s

second attempt, the PTO instituted the interference proceeding that is

the basis of the present appeal. Appx456-463.

H. The Board Rules in Favor of Ho on the Motions of No


Interference-in-Fact and Lack of Written Description

The Board instituted the interference proceeding based on one

count, which was an alternative of claim 1 of the Furcht ‘118 patent,

claim 124 of the Furcht ‘256 application, claim 1 of the Furcht ‘037

patent, claim 1 of the Ho ‘685 application, or claim 14 of Ho ‘244

application. Appx456-463. These claims read as follows:

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Claim 1 (Furcht ‘118 patent): A cell culture comprising


isolated expanded human multipotent, nonembryonic, non-
germ cells that can differentiate into at least one cell type of
each of the endodermal, ectodermal, and mesodermal
embryonic lineages and express telomerase, said cells having
undergone at least 10-40 cell doublings in culture.

Claim 124 (Furcht ‘256 application): A human cell


population that has undergone 22 cell doublings in culture
that expresses CD90 and CD49c and one or more of sox-9,
sox-11, hox-A5, and MSX-1.

Claim 1 (Furcht ‘037 patent): An isolated cell population


derived from human bone marrow, wherein the cells of the
cell population co-express CD49c and CD90, and wherein the
cell population has a doubling rate of about 36 hours.

Claim 1 (Ho ‘685 application): An isolated cell population


induced to express at least one cardiac-related transcription
factor, wherein the cell population is derived from bone
marrow, wherein greater than about 91% of the cells of the
cell population co-express CD49c and CD90, and wherein the
cell population is capable of maintaining a doubling rate of
less than about 30 hours after 30 cell doublings.

Claim 14 (Ho ‘244 application): An isolated cell population


derived from human bone marrow, wherein greater than
about 91% of the cells of the cell population co-express
CD49c and CD90, and wherein the cell population maintains
a doubling rate of less than about 30 hours after 30 cell
doublings.

Appx4-6.

During the interference proceeding, each party presented

testimony from expert witnesses, which the Board fully considered. See

Appx9-12. Ho filed two declarations from Dr. Donald Phinney.

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Appx2416-2438; Appx2940-2968. Furcht submitted one declaration

from Dr. Armand Keating. Appx2383-2411. The parties also relied on

the Deans Declarations and the Kopen Declaration. Appx2459-2496;

Appx2541-2573. Each witness was subject to cross-examination.

Appx1834-1862 (Phinney); Appx1863-2032 (Kopen); Appx3925-4161

(Deans); Appx4162-4434 (Keating).

After briefing and oral hearing, the Board ruled that the Furcht

claims were not patentable because they were not adequately supported

under 35 U.S.C. § 112. Appx25-33. The Board also ruled that there

was no interference-in-fact. Appx33-44. The Board did not reach the

issues of whether the Furcht claims were enabled under § 112 and the

issue of doubling rate. Appx47-50.

The Board ruled that Furcht had failed to demonstrate that over

91% of the cells of the Furcht specification co-express CD49c and CD90.

Appx16. The Deans Declarations—offered as proof of interfering

subject matter—did did not provide evidence of the stem cells disclosed

in the Furcht application and thus did not establish written description

support for the CD49c/CD90 limitation. Appx16-24.

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The Board first recognized that the Furcht specification does not

“explicitly describe[] a product wherein greater than about 91% of the

cells of the cell population co-express CD49c and CD90.” Appx22.

Thus, there was no express written description to support the Furcht

‘037 claims. Appx22. Next, the Board turned to whether the Furcht

disclosure inherently described cells that co-express CD49c and CD90

over 91%. Id. The Board concluded in the negative. Id.

Here, the Board considered the detailed testimony of the expert

witnesses. The Board found the “testimony by Dr. Phinney and Dr.

Kopen (albeit a named inventor) to be highly credible.” Appx22. The

Board also determined that the Deans Experiments were not

representative of the cells described in the Furcht specification because

there were at least five differences, or variations, between the Deans

Experiments and the Furcht example. Appx22-24.

The Board found that there was a “different means . . . used to

remove the red blood cells.” Id. There was also “a difference in medium

used to culture cells,” and the Board had “not been told why use of

medium ‘one’ in place of medium ‘two’ would produce the same results.”

Id. (emphasis in original). The Board also noted that there was a

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difference in oxygen content, observing that Furcht had not established

that “a test at 5% oxygen will yield the same result as a test at ~20%

oxygen.” Appx23. The Board also agreed that the differences in the

immunodepletion step and the type of culturing vessel were significant

for the reasons given by Ho’s witnesses. Appx24. In view of the

material differences, the Board ruled that the evidence did not

demonstrate that the cells described in the Furcht application actually

express both CD49c and CD90 over 91%. Appx16.

The Board also ruled that the claims of the Furcht ‘118 patent

were not adequately supported by the written description. Appx28-33.

The Board held that “Furcht ‘118 claim 1 is broad enough to include cell

cultures isolated from” marrow, liver, or brain, and that the

specification did not provide adequate working examples to support

such a broad claim in stem cell technology, which “was in its infancy

and was highly unpredictable.” Appx29-30.

The Board also found that claim 124 of the Furcht ‘256 application

lacks a written description. Appx33. The Board observed that Furcht’s

opposition was “essentially the same as its opposition with respect to

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Furcht ‘037 claim 1” and thus ruled in favor of Ho for the same reasons.

Appx33.

Finally, the Board held that there was no interference-in-fact

between any Furcht claim and any Ho claim. Appx33-44. The Board

again detailed the substantial differences between the claimed subject

matter, as well as the deficiencies in Furcht’s evidence. Appx33-44.

SUMMARY OF THE ARGUMENT

ABT rests its appeal primarily on challenges to the Board’s fact

findings. ABT’s challenges should be rejected because, based on the

extensive evidentiary record, substantial evidence supports the Board’s

decision.

First, substantial evidence supports the Board’s decision about the

level of skill in the art. The Board found little difference between the

definitions offered by Dr. Phinney and Dr. Keating. Even if there were

a difference, ABT never explains how the purported “critical” error

demonstrates reversible error.

Second, substantial evidence supports the Board’s finding that

stem cell technology was an unpredictable art during the relevant time.

Dr. Phinney’s testimony directly addressed the unpredictability.

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Numerous references describe the uncertainty about the techniques

used for stem cell isolation and culturing. Even publications by

Furcht’s inventors and experts evince the unpredictability. The

incident concerning falsified data epitomized the need for detailed

guidance due to the uncertainty in stem cell science at the time.

Third, substantial evidence supports the Board’s decision to give

more credit to the testimony of Garnet’s experts over ABT’s experts.

ABT’s expert Dr. Keating acknowledged a lack of unfamiliarity with

important facts relating to the issues. Additionally, his declaration was

conclusory and lacked documentary support.

Fourth, substantial evidence supports the Board’s decision that

the claims of the Furcht ‘037 patent are not adequately described.

During the interference, ABT attempted to establish inherent written

description for a stem cell population co-expressing CD49c and CD90 by

relying on the Deans Experiments. As the Board found, however, the

stem cells produced by Deans Experiments were not representative of

the stem cells disclosed in the Furcht specification.

Fifth, substantial evidence supports the Board’s decision that the

broad generic claims of the Furcht ‘118 patent are not adequately

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described. The ‘118 patent attempts to claim a stem cell population

that can be obtained from almost any type of human cell and that has

the ability to differentiate into almost any type of human cell. The

Board correctly found that the single example provided in the ‘037

specification was not an adequate written description under 35 U.S.C.

§ 112. The extensive factual record includes substantial evidence to

support the Board’s finding.

Sixth, ABT’s challenge regarding the Furcht ‘256 application

merely repeats its earlier disagreements with the Board’s factual

findings. ABT’s challenge should be rejected for the same reasons.

Finally, ABT’s appeal of the Board’s decision concerning no

interference-in-fact is entirely dependent on ABT’s arguments

concerning written description. The Board’s decision therefore should

be affirmed for the same reasons.

ARGUMENT

I. Standard Of Review

The Board’s factual findings are reviewed under the deferential

substantial evidence standard. In re Gartside, 203 F.3d 1305, 1311

(Fed. Cir. 2000). Whether the written description requirement is met is

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a question of fact, reviewed by this Court for substantial evidence.

Bamberg v. Dalvey, 815 F.3d 793, 797 (Fed. Cir. 2016); Harari v. Lee,

656 F.3d 1331, 1340 (Fed. Cir. 2011); Chen v. Bouchard, 347 F.3d 1299,

1304 (Fed. Cir. 2003).

Substantial evidence “means such relevant evidence as a

reasonable mind might accept as adequate to support a conclusion.”

Consol. Edison Co. v. NLRB, 305 U.S. 197, 229 (1938). “[T]he

possibility of drawing two inconsistent conclusions from the evidence”

will not render the Board’s findings unsupported by substantial

evidence. See Consolo v. Fed. Mar. Comm’n, 383 U.S. 607, 620 (1966).

If the evidence supports more than one reasonable but contradictory

conclusion, the Board’s decision will not be overturned merely because

the Board opted for one reasonable finding over a different reasonable

finding. In re Jolley, 308 F.3d 1317, 1320 (Fed. Cir. 2002).

II. The Board Did Not Adopt Or Rely On An “Improper” Definition Of


The Level Of Ordinary Skill In The Art

On appeal, ABT first contends that the Board adopted an

“improper” definition of the level of ordinary skill in the art. Appellant

Br. 25-26. ABT’s arguments are misplaced, and they offer no basis for

reversal.

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First, the question of the level of ordinary skill in the art is a

question of fact. See, e.g., Graham v John Deere Co., 383 U.S. 1, 17

(1966); Dystar Textilfarben GmbH v. C.H. Patrick Co., 464 F.3d 1356,

1360 (Fed. Cir. 2006). Thus, the Board’s finding must be sustained if

the record contains substantial evidence. Gartside, 203 F.3d at 1311.

In its brief, ABT does not state that the Board’s factual

determination on the level of ordinary skill is unsupported by

substantial evidence. See Appellant Br. 25-26. ABT merely argues that

“Furcht’s experts submitted that the level of skill in the art was quite

high, whilst Ho’s experts argued that the level of skill was rather low.”

Appellant Br. 16. Furcht further contends there was a “more

appropriate definition of one or ordinary skill in the art.” Appellant Br.

26. The existence of an alternative, “more appropriate” fact-finding

does not mean the Board’s factual conclusion lacks substantial evidence.

Importantly, there is no meaningful distinction between the two

definitions. The two experts’ definitions, in the Board’s view, did not

“differ all that much when defining the level of skill in the art.”

Appx13. Both Dr. Phinney and Dr. Keating required the person of

ordinary skill in the art to have a Ph.D. in biology or a related

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discipline. Appx12. Both experts required the person of ordinary skill

to have advanced technical knowledge about culturing stem cells and

experience characterizing stem cells. Appx12.

ABT is incorrect when it argues that Dr. Phinney’s definition does

“not even requir[e] experience with stem cell cultures.” Appellant Br.

26. The Board expressly rejected this argument. Appx13 (“Dr. Phinney

includes within the skill of the art an ability to perform routine [tasks]

based on the knowledge that existed with respect to culturing stem

cells.”). Dr. Phinney required that the person of ordinary skill “would

have been able to perform routine trouble shooting tasks based on the

knowledge that existed at the time with respect to culturing stem cells

or other primary mammalian cells, and have a basic understanding of

[the] method used to characterize the physical and biological properties

of mammalian stem cells.” Appx12. Dr. Phinney’s extensive experience

with stem cells gives him significant familiarity with what a person of

ordinary skill in the art would know. See Appx2439-2458.

Even if there were a meaningful difference between the two

definitions, ABT does not demonstrate any harmful error based on the

purported incorrect level of skill in the art. ABT only generally claims

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that “[t]he Board’s erroneous finding regarding the skill in the art

tainted all of its subsequent findings as to written description and

interference-in-fact.” Appellant Br. 18. ABT does not explain with any

specificity how any purported difference between the definitions of the

level of skill caused the Board to reach an incorrect legal decision or an

unsupported factual finding. ABT’s generalized complaint is not

sufficient to demonstrate a reversible error in the Board’s factual

findings or legal holding. The Board explained that, in the experts’

testimony, “reference is made to scientific documents supporting their

respective positions” and “[t]hose document[s] facially provide sufficient

evidence revealing what one skilled in the art would have known.”

Appx13.

In sum, while ABT asserts that “[t]he level of ordinary skill in the

art is critical to the case,” Appellant Br. 25, ABT does not articulate the

alleged criticality. The Board’s decision concerning level of skill in the

art is correct and is supported by substantial evidence.

III. The Board Did Not Err In Crediting The Testimony of Ho’s
Experts Over Furcht’s Experts

Furcht next argues that the Board credited the testimony of Ho’s

experts over that of Furcht’s experts. See, e.g., Appellant Br. 14, 16-17.

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To the extent the Board weighed the expert testimony, the Board did

not err. See Newell Cos., Inc. v. Kenney Mfg. Co., 864 F.2d 757, 787-88

(Fed. Cir. 1988) (“Determining the weight and credibility of the

evidence is the special province of the trier of fact.”) Furcht also does

not explain how any purported error here requires reversal.

Cross-examination of Furcht’s primary expert witness, Dr.

Armand Keating, revealed significant weaknesses in his testimony. See

Appx3925-4162. Dr. Keating exhibited limited knowledge about the

subject matter of the Furcht patent, which are purportedly MAPCs:

Q. Getting back to the topic of MAPCs, do you know whether


there are different types of MAPCs?

A. I do not know the answer to whether or not there are


different types of MAPCs.

Appx4191-4192. He also did not know significant details about the

development of MAPCs:

Q. Okay. I’m not an expert in this area, so I might be using


the wrong terminology, but does a does an embryonic stem
cell turn directly into a MAPC?

A. I do not know the answer to if an embryonic stem cell


turns into a MAPC.

Appx4191-4192.

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Dr. Keating acknowledged that he read only “[o]ccasional articles

with respect to MAPC research,” he never published articles directed to

MAPCs, and he had never grown or isolated MAPCs in his lab.

Appx4259; Appx4193; Appx4265 (“no personal experience” with

MAPCs). He did not know whether MAPCs “exist in the human body

and are isolated through a particular process.” Appx4272.

Dr. Keating also stated that he was “not aware of any literature

that addresses the issue of atmosphere on cell surface antigen

expression, cell surface protein expression.” Appx4196. Yet, numerous

articles in the field detailed the effect of oxygen content in the

atmosphere to the effect on protein expression, even his own. See

Appx3396 (article listing Dr. Keating and Dr. Deans as authors:

“[m]aintaining a hypoxic environment” is an important parameter for

culturing stem cells); Appx3374 (article by Dr. Keating identifying

“oxygen tension” as one of several factors affecting the stem cell

manufacturing process); see also Appx4273-4299.

Dr. Keating’s cross-examination revealed significant gaps in his

knowledge about the cell surface proteins that are purportedly

indicative of MAPCs.

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Q. Right. Okay. Do you know what CD13 does? It’s listed in


the “Cell surface phenotype.”

A. I would have to familiarize myself with CD13.

Q. Do you know what CD73 does?

A. I’m familiar with CD73, but I not sure I really understand


its role.

Q. Okay. And can you tell me anything about CD146 with


respect to MAPCs?

A. I’m not sure that I’m able to do that. It is considered a


marker of stromal cells.

Appx4257. He did not know whether CD90w is the same as CD90.

Appx4325. These proteins were identified as potential markers for

various stem cells. See Appx2955.

Dr. Keating was also unaware that Verfaille’s Blood paper had

been retracted due to the falsified data. Appx4249; Appx4357-4363.5

He did not know whether any other scientific group was able to

replicate Dr. Verfaille’s research. Appx4261-4262. His lack of

knowledge is important because it directly addresses the question of

whether a person of ordinary skill in the art would view stem cell

technology as unpredictable. Dr. Keating was simply unaware of key

5 The copy of the Blood article Furcht submitted as an exhibit,


Appx1653-1663, omits the notice of retraction, which is in the copy
submitted by Ho, Appx3200-3212.

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information that corroborated the high level of unpredictability in the

stem cell field.

Similarly, Dr. Deans, who testified on behalf of Furcht, was

evasive in response to numerous questions. Appx4045 (being unable to

explain what he meant by “reasonably expected”); Appx4036-4040;

Appx4092-4093. Dr. Deans appeared insufficiently prepared for his

cross-examination; he stated that he had not reviewed “in scientific

detail” certain of cited exhibits prior to his cross-examination.

Appx4050; Appx4096 (responding that it would take Dr. Deans a

“significant block of time” to read the ‘037 patent and determine

whether the Furcht method uses a T75 flask).

Finally, in its opening brief, ABT offers no reason to discredit the

testimony of Garnet’s experts. The testimony of Dr. Phinney and Dr.

Kopen was highly credible, and ABT cannot challenge their testimony

for the first time in its reply brief. See, e.g., Sage Prods., Inc. v. Devon

Indus., Inc., 126 F.3d 1420, 1426 (Fed. Cir. 1997) (“With a few notable

exceptions, such as some jurisdictional matters, appellate courts do not

consider a party’s new theories, lodged first on appeal.”).

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Based on the testimony as a whole, the Board acted well within its

discretion to credit the testimony of Garnet’s experts over ABT’s

experts. See Velander v. Garner, 348 F.3d 1359, 1371 (Fed. Cir. 2003)

(“In giving more weight to prior publications than to subsequent

conclusory statements by experts, the Board acted well within that

discretion.”); Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776

F.2d 281, 294 (Fed. Cir. 1985) (“Lack of factual support for expert

opinion going to factual determinations, however, may render the

testimony of little probative value in a validity determination.”).

IV. The Board Correctly Found That Stem Cell Technology Was
Unpredictable in 1999-2000

ABT next advances general disputes about the Board’s findings on

the state of the art. See Appellant Br. 26-28, 41-44. ABT’s complaints

are linked to its challenge to both the written description and no

interference-in-fact issues. ABT’s complaints have no merit because the

evidence demonstrates unpredictability.

ABT’s primary argument on appeal is that the Board purportedly

made “erroneous findings regarding the state of the art.” Appellant

Br. 41. As ABT notes, the Board found that the “state of the art of the

claimed inventions was ‘a rapidly evolving field full of uncertainties,’

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and ‘in its infancy and . . . highly unpredictable.’” Appellant Br. 42

(citing Appx29-30).

ABT expressly reverses the correct inquiry. ABT argues that,

“despite substantial evidence to the contrary,” the Board found

unpredictability with the mouse model. Appellant Br. 42 (citing

Appx31). The existence of “substantial evidence to the contrary” is not

dispositive. The pertinent question is whether substantial evidence

supports the Board’s findings. ABT can prevail only by showing a lack

of substantial evidence supporting those findings. See Consolo, 383

U.S. at 620. For the most part, ABT simply fails to contend that the

Board’s findings lack substantial evidence support.

Importantly, the record is replete with evidence about the

unpredictability of stem cell research during the relevant time period of

1999-2000 and beyond. Dr. Phinney explained that the state of the art

at the relevant time period was extremely unpredictable. Appx2945

(“In 1999 and 2000 stem cell research was a rapidly evolving field with

many uncertainties that gave rise to intense debate among scientists.”);

Appx2948 (“[C]ell culture methods were highly unpredictable in the

hands of an ordinarily skilled artisan.”); Appx2947 (“In 1999 and 2000

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MSCs were not well defined with regard to phenotype and function.”).

Even a 2014 article co-authored by Furcht’s experts Dr. Keating and

Dr. Dean explains that “[p]ersistent issues include the definition of a

MSC and comparability between MSC preparations.” Appx3391. ABT

does not address this evidence on appeal.

Dr. Keating’s testimony is not to the contrary. If anything, Dr.

Keating’s uncertainty in answering many questions during his cross-

examination only underscores the unpredictability in the art. He did

not know, for example, that Dr. Verfaille had to change experimental

conditions over the years in order to isolate the MAPCs. Appx4254-

4255.

ABT also makes little reference to the data falsification associated

with Verfaille’s MAPC work. The data falsification and the errors

associated with publications and patent applications illustrate the

uncertainty in the stem cell field. Appx2957 (“Those working in the

field in 1999-2000 would consider such falsification to significantly

harm the credibility of the inventors with regard to the reproducibility

and validity of the experiments, Examples and supporting figures set

forth in the ‘037 patent.”). ABT’s expert Dr. Keating acknowledged

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that, because of the falsification of data, “there might be additional

skepticism” by a stem cell scientist. Appx4348. The continued

problems experienced by Verfaille and others in isolating the MAPCs,

which are the cells in the Furcht specification, constitute substantial

evidence that the field was unpredictable in 1999. See Enzo Biochem,

Inc. v. Calgene, Inc., 188 F.3d 1362, 1372 (Fed. Cir. 1999).

ABT also argues that the unpredictability in the art was limited to

“the culture conditions required to cause the stem cells to differentiate

into various downstream lineages, and not to the culture conditions

required to obtain the stem cells.” Appellant Br. 42. ABT does not

support its contention with any citation to the record evidence. See id.

Regardless, it is not correct because the evidence demonstrates general

unpredictability.

The only specific argument ABT asserts—again without any

citation to record evidence—is that the Board’s reliance on a 1997

article by Brewer, Appx3108-3120, is not reflective of the state of the

art two years later, in 1999. See Appellant Br. 43. The two-year

difference is of no consequence because the evidence of record shows

significant unpredictability both before and after the relevant time

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period. Appx2945-2950 (citing Appx3108-3172); Appx3044-3107;

Appx3793 (Verfaille in 2004: “Currently we do not fully understand the

mechanism(s) underlying the culture selection of MAPC.”).

Accordingly, the Board’s finding that stem cell technology was

unpredictable in 1999 finds support in substantial evidence, and ABT

does not identify any basis to disturb this finding.

V. Substantial Evidence Supports The Board’s Finding That The


Furcht ‘037 Claims Are Not “Inherently” Described In The Furcht
Specification

The specification of Furcht’s 037 patent does not expressly

describe the limitation that the stem cells co-express greater than 91%

CD49c and CD90. Thus, the issue in dispute is whether Furcht has met

its burden in proving that its specification inherently describes the “co-

express” limitation Furcht copied from the Ho applications. Hyatt v.

Boone, 146 F.3d 1348, 1353-54 (Fed. Cir. 1998); Martin v. Mayer, 823

F.2d 500, 505 (Fed. Cir. 1987); DeGeorge v. Bernier, 768 F.2d 1318,

1321 (Fed. Cir. 1985) (“[T]he party copying the claims . . . had the

burden of persuasion on the right to make the counts which had to be

met before an interference could properly be declared.”).

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ABT advances four general arguments as to why the Board’s

decision on “inherent written description” of the ’037 patent claims is

allegedly erroneous. Appellant Br. 23-41. First, ABT argues that the

Board erred concerning the level of skill in the art. Id. at 25-26.

Second, ABT argues that the Board’s decision concerning the

unpredictability in the art is wrong. Id. at 26-28. Third, ABT argues

the Board misconstrued the meaning of “co-express.” Id. at 28-34.

Fourth, ABT disagrees with the Board’s findings concerning the

differences between the Deans Experiments and the Furcht application

method. Id. at 35-41. The first two arguments should be rejected for

the reasons presented above. The second two arguments should be

rejected for the reasons presented below.

A. Legal Standard for the Written Description Requirement

“The basic function of a patent specification is to disclose an

invention.” Carnegie Mellon Univ. v. Hoffmann-La Roche, Inc., 541

F.3d 1115, 1122 (Fed. Cir. 2008). A patentee “can lawfully claim only

what he has invented and described, and if he claims more his patent is

void.” O’Reilly v. Morse, 56 U.S. (15 How.) 62, 121 (1853).

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The written description’s purpose is to serve as a quid pro quo

through “which the public is given ‘meaningful disclosure in exchange

for being excluded from practicing the invention for a limited period of

time.’” Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 922

(Fed. Cir. 2004) (quoting Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d

956, 970 (Fed. Cir. 2002)).

A patent “does not have to utilize any particular form of disclosure

to describe the subject matter claimed, but the description must clearly

allow persons of ordinary skill in the art to recognize that he or she

invented what is claimed.” In re Alton, 76 F.3d 1168, 1172 (Fed. Cir.

1996) (quotations omitted). The applicant must “convey with

reasonable clarity to those skilled in the art that, as of the filing date

sought, he or she was in possession of the invention.” Vas-Cath Inc. v.

Mahurkar, 935 F.2d 1555, 1564 (Fed. Cir. 1991); Univ. of Rochester, 358

F.3d at 926 (“The specification must teach the invention by describing

it.”).

In sum, the written description requirement ensures that the

inventor has actually invented what he or she has claimed. When broad

claims are presented in unpredictable arts, such as stem cell

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technology, the claims must be supported by adequate examples—not a

single example—in order to satisfy the written description requirement.

B. The Board Correctly Identified Significant Differences


Between the Methods Used in the Deans Experiments and
the Method Used in the Furcht Application

The Board found five significant differences between the methods

used in the Deans Experiments and the method used in the Furcht ‘037

patent to produce the respective stem cell populations. Appx15-24.

Because of these differences, the stem cell populations produced by the

Deans Experiments was not the same as described and made in the

Furcht specification. Appx25-28; Appx2961. These findings are fully

supported, and ABT has not shown the absence of substantial evidence.

First, the Board correctly found that removing red blood cells from

the culture by Ficoll-Paque, as used in Furcht Example 1, is

significantly different than using an ammonium chloride process, as

described in the Ho applications. Appx17-18. The record evidence

confirms that the identity, e.g., protein expression, of the stem cell

population is highly dependent on whether and how red blood cells are

removed. Appx2960; Appx2949-2954. Dr. Phinney’s testimony detailed

the difference between the Deans Experiments and the Furcht example,

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explaining that the Deans Declarations were silent on this step.

Appx2960 (“omitting the negative selection step, which removes 99.90-

99.95% of the original bone marrow cells”). Thus, “[a]ny conclusions

regarding the co-expression of CD49c and CD90 on the cells made by

the methods of the Deans Declaration or the second Deans Declaration .

. . would have no bearing on whether the cells made using the methods

disclosed in the ‘037 patent claims had such expression.” Appx2961.

In contrast, Dr. Keating’s testimony was conclusory and without

explanation. He merely stated in his declaration: “Removing red blood

cells from the culture: The choice of using Ficoll-Paque gradient

centrifugation, Histopaque separation or lysis (ammonium chloride)

would not be expected to produce significantly different results.”

Appx2395. An expert’s bare statement cannot overcome the weight of

the evidence demonstrating that the method of removing blood cells will

significantly affect the stem cell population. See Velander, 348 F.3d at

1371 (“In giving more weight to prior publications than to subsequent

conclusory statements by experts, the Board acted well within that

discretion.”).

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Second, the Board correctly found that removing CD45-positive

cells, as described in the Furcht Example 1, is significantly different

than what was done in the Deans Experiments. Appx18. Again,

Dr. Phinney detailed this particular difference. Appx2422-2423;

Appx2961. He also explained the importance of this difference during

his cross-examination. Appx1984-1985.

ABT alleges only that “the Board failed to consider Dr. Keating’s

reference to a publication by Baddoo.” Appellant Br. 36 (citing

Appx1588-1602). Nothing indicates that the Board ignored the

testimony or the cited reference. Dr. Keating’s testimony adds little, as

he merely referred to Baddoo in a single sentence, stating that Badoo

“shows that all of immunodepletion, ammonium chloride lysis and Ficoll

gradient separation can be used to enrich CFU-F and deplete

hematopoietic progenitors.” Appx2395. The issue is not whether the

three procedures can be used but whether the three procedures yield

different results. ABT does not contend that Dr. Keating testified that

the methods are equivalent.

Third, the Board correctly concluded that the composition of the

cell culture medium would significantly affect the identity of the stem

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cell population. Appx19. Dr. Phinney explained that the composition of

the cell culture medium is important and that the cell culture media

differed significantly between the Deans Experiments and the Furcht

example. Appx2960-2961; Appx1985-1985; Appx4102-4108. In the

second Deans Declaration, Dr. Deans used a cell culture medium of

unknown composition. Appx2960; Appx4099-4102.

Numerous references detail the effect of cell culture medium on

the identify of progenitor cell populations. E.g., Appx2958-2963. ABT

does not address this evidence in its brief.

Fourth, the Board correctly found that there was a significant

difference between the 5%-oxygen condition used in the Deans

Declarations and the 21%-oxygen used in Furcht Example 1. The

record is replete with testimony and documents establishing that the

difference in oxygen content for culturing stem cells will significantly

affect the identity and protein makeup of the cell. See, e.g., Appx3287;

Appx4273-4299 (discussing Appx1664-1670, Appx1684-1692, Appx1703-

1714, Appx1721-1739). ABT again does not address the multiple

references supporting the finding that oxygen levels affect the identity

of the stem cells and the expression of cellular proteins.

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ABT’s misplaced argument is revealed by its statement: “Dr.

Deans showed that when the Furcht cells were grown under low oxygen

conditions . . . .” Appellant Br. 38. ABT’s statement reveals its error;

Dr. Deans never grew the Furcht cells because it used a different

oxygen level. During his cross-examination, Dr. Deans acknowledged

that oxygen content can change protein expression on stem cells.

Appx4023; see also Appx4047-4049; Appx-4056-4065 (discussing

Appx1684-1692 and Appx1703-1714); Appx4067-4076 (discussing

Appx1715-1752); Appx4083-4085 (discussing Appx1797-1810);

Appx4087-4092 (discussing Appx3285-3296). The evidence establishes

that oxygen levels alter a stem cell’s expression of cellular proteins,

including CD49c and CD90. Appx22-23.

Fifth, the Board correctly found that significant differences

existed because the Deans Experiments used a T75 flask, while the

Furcht Example 1 used a 96-well plate. Appx21; Appx24. The evidence

described the significant differences one would expect in stem cell

populations based on the type of vessel used. Appx2960-2961.

Dr. Phinney testified about these differences during his cross-

examination. Appx1984-1985. He detailed how the method used in the

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Ho application uses a T75 flask and that “this is a large culture vessel

and so that typically indicates that the cells are not as sensitive to the

microenvironment with respect to the growth because you add large

amounts of media and would dilute out any growth factors produced by

the cells themselves and that speaks to the different biological

properties of the cells.” Appx1984-1985. He further explained that, in

contrast, the Furcht application used 96-well plates having a “small

surface area” and that “one would use that approach when trying to

isolate a rare cell because that small volume well provides a

microenvironment where the rare cell can condition its own media and

that’s usually thought to promote the survival and eventual expansion

of that cell.” Appx1985. ABT overlooks this testimony on appeal.

ABT’s expert Dr. Keating offered only a single conclusory

statement on whether the type of vessel would affect the type of cell

obtained, without any consideration of the cited technical documents.

Appx2395. While he stated that “[o]ne would not expect a significant

difference in cells grown in six well plates or T-75 flasks,” he did not

explain why and he did not support his conclusion with any

documentary evidence. Dr. Deans, on the other hand, acknowledged

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that “[t]he relationship of seeding density to surface area can be a

variable in establishing the culture” and that “Furcht teaches the

criticality of cell density in plating and retention of the MAPC

phenotype.” Appx4098-4099.

Finally, ABT contends that “[t]he Board essentially ignored the

data in the Deans declaration.” Appellant Br. 35. That complaint has

no basis. The Board carefully considered the evidence but rejected

ABT’s view of the evidence. ABT’s narrow factual challenges on appeal

do not establish the absence of substantial evidence.

In sum, ABT has not identified a single fact finding for which

substantial evidence is lacking. ABT instead asks this Court to reweigh

the evidence and make factual findings anew. Substantial evidence

supports the Board’s findings that there were significant differences

between the method used in the Deans Declarations and the method in

the Furcht specification. Therefore, there is substantial evidence that

the Deans Experiments do not accurately reflect the cells described in

the Furcht ‘037 patent and therefore Furcht has not shown “inherent

written description” of the “co-expressing CD49c and CD90” claim

limitation.

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C. The Board Did Not Misconstrue the Definition of “Co-


Express”

ABT also contends that the Board misconstrued the proper scope

of the term “co-express.” Contrary to ABT’s argument, the Board’s

claim construction is correct, and the fact findings supporting the

Board’s construction rest on substantial evidence.

With respect to the ‘037 patent, Furcht copied Ho’s claims in this

interference. Appx2593-2605 (stating the new claims were “substantial

copies of pending claim 14 of the Ho’ 244 application”). The claims are

thus given their broadest reasonable construction in light of the ‘244

specification. Harari, 656 F.3d at 1340; see also Agilent Techs., Inc. v.

Affymetrix, Inc., 567 F.3d 1366, 1375 (Fed. Cir. 2009) (“[W]hen a party

challenges written description support for an interference count or the

copied claim in an interference, the originating disclosure provides the

meaning of the pertinent claim language."); In re Spina, 975 F.2d 854,

856 (Fed. Cir. 1992) (“When interpretation is required of a claim that is

copied for interference purposes, the copied claim is viewed in the

context of the patent from which it was copied.”).

“[U]nder the broadest reasonable interpretation, the Board’s

construction cannot be divorced from the specification and the record

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evidence, and must be consistent with the one that those skilled in the

art would reach.” Microsoft Corp. v. Proxyconn, Inc., 789 F.3d 1292,

1298 (Fed. Cir. 2015) (internal quotations and citations omitted).

“The terms used in patent claims are not construed in the

abstract, but in the context in which the term was presented and used

by the patentee, as it would have been understood by a person of

ordinary skill in the field of the invention on reading the patent

documents.” Fenner Invs., Ltd. v. Cellco P’ship, 778 F.3d 1320, 1322-23

(Fed. Cir. 2015); see also Biogen Idec, Inc. v. GlaxoSmithKline LLC, 713

F.3d 1090, 1095 (Fed. Cir. 2013) (“[A] term’s ordinary meaning must be

considered in the context of all the intrinsic evidence, including the

claims, specification, and prosecution history.”).

Here, the Board correctly construed the term “co-express” when

considering the evidence as a whole. Ho’s expert Dr. Phinney testified

that “co-express” has a “well-defined” meaning for scientists working in

the stem cell field. Appx1969-1971.

Q. If you recall from earlier today, Mr. Huntington was


asking you about the meaning of co-express as it is used in
the Ho applications. Do you recall that?

A. Yes.

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Q. Is the term co-express something that’s well-defined in


the art of stem cell research?

A. Yes.

Q. And what’s the general understanding of that term?

A. Particularly as it applies to flow cytometric analysis using


cluster designation antigens, it’s typically interpreted as it is
in the Ho [application], which is a single cell simultaneously
expresses or co-expresses two proteins.

Q. So if there is a description that the cell co-expresses


CD49c and CD90, how would one of ordinary skill in the art
interpret that?

A. One would interpret it to mean that if you did double


staining on a population of cells, at least some measurable
number would co-express both antigens.

Q. Are you aware of any articles that use co-express in a


manner contrary to the definition as it’s understood in the
field?

A. Not based on my recollection at this time.

Q. Now, if you read an article or even patent application, and


it defined co-express differently, would you require any
additional information to believe that different meaning of
the term co-express?

A. Yes. It would have to demonstrate that their definition is


valid in the sense you can have a measurable outcome.

Q. And by measurable -- measurable outcome, what do you


mean?

A. That they can demonstrate or illustrate their definition of


co-express.

Q. And how would one do that?

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A. Through some experimentation.

Q. And which experimentation specifically?

A. Typically, as we noted, surface expression of proteins is


determined using flow cytometry.

Appx1969-1971. ABT does not address this testimony on appeal, and

the testimony supports the Board’s construction.

ABT’s argument rests on language in the Ho ’685 application

which ABT believes expands the art-accepted definition of “co-express.”

See Appellant Br. 28-30. Contrary to ABT’s argument, the wording in

the ‘685 application does not change how a person of ordinary skill in

the art would understand the term “co-express.” ABT does not identify

any additional disclosure in the specification indicating the inventors

intended to expand the definition of “co-express.” See Appellant Br. 29-

30.

In a footnote, ABT cites a portion of Dr. Phinney’s testimony, but

his complete testimony confirms the Board’s construction. Dr. Phinney

expressly confirmed the Board’s construction:

Q. Wouldn’t saying alternatively on or in a collection of cells


would allow for CD49c to be on certain cells and CD90 to be
on others?

A. Not when the term co-express is used and defined as such.

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Q. So what does the phrase alternatively on or in a collection


of cells add to the rest of the definition?

A. My interpretation is it means it can be more than one cell


so that you could simultaneously detect both proteins on a
single cell or more than a single cell in a collection of cells.

Appx1914-1915. ABT overlooks this testimony on appeal, and ABT is

incorrect when asserting that Dr. Phinney “admitt[ed] that the

definitions in the two Ho applications conflicted.” See Appellant Br. 29

n.7.

Similarly, Dr. Keating’s conclusory testimony does not support

ABT’s argument. Dr. Keating offered only a single paragraph in which

he merely “disagree[d]” with Dr. Phinney’s view. Appx2394. He cited

only one of the Deans Declarations, but that document does not explain

how the term “co-express” is to be understood. The Board observed that

“Deans does not explain in his declarations how [the figure depicting

the data] supports his opinion that well over 91% of the tested cells

expressed both CD49c and CD90.” Appx16. Beyond that, Dr. Keating

identified no document or technical article to support for his position.

Finally, ABT’s reliance on the ‘685 application is misplaced

because claim 1 of the Furcht ‘037 patent copied the “co-express”

limitation from the Ho ‘244 application. Appx2597. Therefore, the ‘244

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application serves as the specification for interpreting the claim. See

Agilent Techs., 567 F.3d at 1375 (“[W]hen a party challenges written

description support for an interference count or the copied claim in an

interference, the originating disclosure provides the meaning of the

pertinent claim language.”); Spina, 975 F.2d at 856 (“When

interpretation is required of a claim that is copied for interference

purposes, the copied claim is viewed in the context of the patent from

which it was copied.”). Thus, even if the evidence supported ABT’s

interpretation—which it does not—it would be irrelevant because the

specification of the Ho ‘244 application controls.

ABT also urges that the Board erred by finding the Furcht ‘037

patent to describe only the presence of mRNA encoding CD49c, and not

the co-expression of the CD49c protein. See Appellant Br. 32-34. The

Board expressly rejected ABT’s argument, Appx27-28, and the finding is

supported by substantial evidence.

The Board relied on a scientific article which explained that the

presence of mRNA does not necessarily mean that the corresponding

protein is expressed in the cell. Appx28 (citing Appx3418-3429). This

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reference by itself is substantial evidence to support the Board’s

decision, and ABT does not address it.

Further, in testimony not cited by ABT, Dr. Keating admitted that

measuring mRNA expression is “not exactly equivalent” to protein

expression, and that he was “not certain” whether a protein is expressed

in a cell when mRNA expression is detected:

Q. So in your view, with respect to this sentence, just


measuring the mRNA expression levels isn’t sufficient to tell
you whether the protein is actually expressed in the cell?

A. Well, it could be.

Q. It could be, but --

A. Yeah.

Q. But you’re not certain?

A. It’s not exactly equivalent.

Q So are you -- with respect to this, are you certain as to


whether the protein is expressed by measuring the mRNA?

A. I’m not certain.

Q. Not certain. Okay.

Appx4271.

Furcht also points to the Ho ‘244 application, but that disclosure

in fact confirms the Board’s finding. The Ho ‘244 application provides

an express definition:

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“Co-express,” as used herein, refers to the simultaneous


detection of two or more molecules, e.g., CD49c and CD90, on
or in a single cell. Techniques to detect co-expression of
CD49c and CD90 in cells (e.g., bone marrow stromal cells)
are well established. For example, co-expression of CD49c
and CD90 on a cell can be detected by multiple color
cytometric analysis. CD49c can be detected employing a
fluorescein labeled probe and CD90 can be detected
employing a Texas red probe. The CD49c and CD90 cell
surface antigens can be visualized with the aid of a flow
cytometer equipped with multiple filters capable of detecting
the multiple colors.

Appx57. The specification then includes the general statement that

“molecules of interest” can be detected by ELISA, RIA,

immunofluorescence microscopy, and quantitative PCR, but it does not

state that CD49c and CD90 can be detected by using all of those

techniques. Id. Nor does the specification provide an example of

detecting CD49c and CD90 using a PCR method.

Even with the mention of PCR, the description is clearly directed

to identifying the CD49c and CD90 proteins themselves, not the mRNA.

To adopt ABT’s reasoning, any cell that has mRNA or DNA encoding

the proteins would be considered a cell “expressing” the proteins, but

Furcht’s own expert Dr. Keating acknowledged that the presence of

mRNA does not “really address the issue of the presence of proteins

themselves.” Appx4293.

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Finally, ABT’s argument regarding Dr. Kopen’s analysis is

erroneous. See Appellant Br. 33-34. ABT cites five pages of Dr. Kopen’s

declaration, but none of those pages addresses mRNA. Appx2544-2549.

That portion of Dr. Kopen’s declaration focuses specifically on expressed

proteins using FACS analysis to identify proteins—similar to the Ho

‘244 and ‘685 applications. Id.

In short, ABT’s argument regarding “co-express” is contrary to the

evidence underlying the Board’s decision. The Board’s claim

construction of “co-express” is legally correct, and substantial evidence

supports the relevant fact findings.

VI. Substantial Evidence Supports The Board’s Finding That The


Furcht ‘118 Claims Do Not Satisfy The Written Description
Requirement

ABT next disputes several factual findings supporting the Board’s

determination that the Furcht ‘118 claims are not adequately described.

Appellant Br. 44-51. One ABT challenge targets the Board’s finding

that the stem cell field was highly unpredictable at the relevant time.

This should be rejected for the reasons detailed above. ABT’s remaining

factual challenges should be rejected for the reasons set forth below.

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A. The Furcht Disclosure Does Not Demonstrate Possession of


the Broadly Claimed Cells

Furcht ‘118 claim 1 reads as follows:

A cell culture comprising isolated expanded human


multipotent, non-embryonic, non-germ cells that can
differentiate into at least one cell type of each of the
endodermal, ectodermal, and mesodermal embryonic
lineages and express telomerase, said cells having
undergone at least 10-40 cell doublings in culture.

Appx28. The Board understood claim 1 of the ‘118 patent to be “broad

enough to include cell cultures isolated from” any organ in the human

body. Appx30-31. On appeal, ABT does not dispute the Board’s

understanding. See Appellant Br. 44-51.

As the Board recognized, claim 1 of the ‘118 patent attempts to

cover cells isolated “from a fetus, newborn, child or adult” and that

“[t]he cell may be derived from an organ, such as from marrow, liver or

brain.” Appx29-30; Appx416; Appx2962. Claim 1 further requires such

isolated cells to be capable of differentiating into at “least one cell type

of each of the endodermal, ectodermal, and mesodermal.” Appx445.

The ‘118 patent therefore attempts to claim a stem cell population that

can be obtained from almost any type of human cell and that has the

ability to differentiate into almost any type of human cell. Id.

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There is no evidence that Furcht invented so broad an invention,

and the single example in the Furcht ‘118 patent does not provide

legally sufficient written description of such a broad claim in the

unpredictable stem cell field. Appx30 (“[T]his case involves a relatively

new and highly unpredictable field where an applicant has described

one species of a rather large genus.”). The patent specification did not

demonstrate possession of an invention in which the claimed cells can

be derived from a fetus, a newborn, or a child. Appx30-33; Appx2962-

2963. The only example disclosed in the Furcht ‘118 patent is the use of

adult bone marrow mononuclear cells to obtain the stem cell culture.

Appx435-436. The inventors provided no other working examples of

isolating cells from a different tissue source.

The Board also noted that claim 1 of the Furcht ‘118 patent is

broad enough to cover a stem cell population derived from any organ

and any cell in the human body—meaning from the approximately 78

human organs and even more types of cells. See, e.g., Appx3143 (listing

“210 varieties of cells” in the human body); Appx2949 (“Bone marrow

contains at least 20 different cells types.” (citing Appx3121-3139)).

Nothing in the specification supports a conclusion that the single

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example is representative of stem cells that could possibly be obtained

from other organs and other cell types. Appx2962-2963.

Dr. Phinney explained in detail why “[i]solation and culture of

cells from bone marrow, brain and liver would require significantly

different procedures and protocols.” Appx2949. Dr. Phinney further

explained that “[s]upporting an assertion that MASCs could be isolated

from each of bone marrow, brain and liver, requires a significant

amount of guidance to establish that cells from all of these sources could

be isolated and could in fact differentiate as asserted” in the Furcht

specification. Appx2949. The Board properly credited this evidence.

B. This Court’s Precedent Supports the Board’s Decision

ABT also takes issue with the Board’s reliance on three specific

cases from this Court’s jurisprudence concerning the written description

requirement as applied to biotechnology inventions. Each case cited by

the Board supports the Board’s fact findings.

As a first point, ABT cannot reasonably dispute that, in an

unpredictable technology area such as stem cell science, a more detailed

disclosure is required to support broad, generic claims. See Ariad

Pharms. Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010) (en banc)

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(“[T]he level of detail required to satisfy the written description

requirement varies depending on the nature and scope of the claims and

on the complexity and predictability of the relevant technology.”);

Capon v. Fisher, 418 F.3d 1349, 1360 (Fed. Cir. 2005) (“The

predictability or unpredictability of the science is relevant to deciding

how much experimental support is required to adequately describe the

scope of an invention.”); In re Fisher, 427 F.2d 833, 839 (C.C.P.A. 1970)

(“In cases involving unpredictable factors, such as most chemical

reactions and physiological activity, the scope of enablement obviously

varies inversely with the degree of unpredictability of the factors

involved.”); The Guidelines for Examination of Patent Applications

under the 35 U.S.C. § 112, ¶ 1, “Written Description” Requirement,

66 Fed. Reg. 1099 (Jan. 5, 2001) (“For inventions in an unpredictable

art, adequate written description of a genus which embraces widely

variant species cannot be achieved by disclosing only one species within

the genus.”), cited with approval by Carnegie Mellon University v.

Hoffmann-La Roche, Inc., 541 F.3d 1115, 1124 (Fed. Cir. 2008).

Second, the Board correctly analogized Furcht’s broad,

unsupported claims to the broad, unsupported claims in the cited three

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cases. In AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc.,

759 F.3d 1285, 1300 (Fed. Cir. 2014), the Court held that “the jury

heard ample evidence that AbbVie’s patents only describe one type of

structurally similar antibodies and that those antibodies are not

representative of the full variety or scope of the genus.” In Ariad, the

Court held that, as a matter of law, the broad generic method claims for

modifying gene expression were not adequately described. 598 F.3d at

1354-58. Similarly, in Carnegie Mellon University, 541 F.3d at 1123-

24, the Court affirmed the invalidity of claims to “recombinant plasmids

that contain a DNA coding sequence that is broadly defined, and only

by its function.” In each instance, broad biotechnology claims were

invalidated under the written description requirement because the

specification lacked sufficient working examples.

The ultimate deficiency with the Furcht ‘118 claims is best

captured by this Court’s explanation of the written description

requirement:

With the written description of a genus, however, merely


drawing a fence around a perceived genus is not a
description of the genus. One needs to show that one has
truly invented the genus, i.e., that one has conceived and
described sufficient representative species encompassing the
breadth of the genus. Otherwise, one has only a research

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plan, leaving it to others to explore the unknown contours of


the claimed genus.

AbbVie, 759 F.3d at 1300. The Furcht ‘118 patent attempts to draw a

fence around a wide swath of stem cell technology—stem cells defined

entirely by function—without disclosing adequate working examples.

See Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568

(Fed. Cir. 1997) (holding that “[a] description of rat insulin cDNA is not

a description of the broad classes of vertebrate or mammalian insulin

cDNA”).

C. The Court Did Not Err Concerning the “Two Facts”


Identified by ABT

ABT also contends that “[t]he Board erred fundamentally in

presuming two facts not found in evidence” regarding the written

description of the ‘118 patent. Appellant Br. 49-51. The record does not

support ABT’s position.

First, the subject matter of the ‘118 claims covers a broad number

of different cells and cell populations, contrary to ABT’s argument. See

Appellant Br. 49-50. There are hundreds of types of cells included in

the genus covered by the claims of the ‘118 patent. Appx2949;

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Appx2963; Appx3121-3139; Appx3141-3144. ABT does not cite any

evidence to the contrary. See Appellant Br. 49-50.

The ‘118 patent claims themselves belie ABT’s argument that the

‘118 patent is directed to “a single product.” Specifically, claim 2

narrows claim 1 by specifying that the cells are “obtained by culture of

non-embryonic, non-germ tissue.” Appx445. Thus, claim 1

encompasses these cell types and others, namely, those “obtained by

culture” of different types of tissue. Accordingly, the plain language

and structure of the claims establish that the ‘118 patent is not directed

to “a single product,” as ABT contends.

Second, the Board correctly found that cells isolated from different

sources are generally of different cell types. The general understanding

in the stem cell field was that stem cells retain differentiation potential

associated with the tissue from which the cells are isolated. Appx2962-

2963 (“To be achievable, a significant amount of detailed disclosure

demonstrating that cells from all sources encompassed by the claims

had been isolated and could in fact differentiate into one cell type of

each of endodermal, ectodermal, and mesodermal embryonic lineages,

would be required.”).

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In sum, the broad claims of the ‘118 patent are not adequately

described and supported by the specification. Indeed, Verfaille and the

other Furcht inventors needed years of additional research to identify

conditions for isolating some of the claimed cells, and there is no

evidence that the full scope of the ‘118 claims has ever been invented.

The Board’s decision is accordingly supported by substantial evidence.

VII. ABT’s Challenge To The Board’s Decision On The Furcht ‘256


Claims Repeats Its Factual Challenges And Should Be Rejected
For The Same Reasons

ABT challenges the Board’s decision that the claims of the Furcht

‘256 application were not adequately described under 35 U.S.C. § 112.

See Appellant Br. 51-54. ABT does not provide a legally sufficient

reason why the Board’s decisions should be overturned.

ABT first asserts that the Board erred by providing a “one

sentence analysis,” but the Board fully considered the issues raised and

detailed its factual findings concerning the lack of examples to support

a broad generic claim. Appx33. Contrary to ABT’s implication, the

Board is not required to reiterate factual findings that it fully set forth

in its decision. The Board noted the similarity of the issues presented

for the Furcht ‘037 patent and agreed that the claims of the ‘256

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application lacked an adequate written description “for the reasons

given above.” Appx33. ABT implicitly acknowledges the propriety of

using an “incorporation-by-reference” approach when it does the same

in its brief. See Appellant Br. 54 (“[T]he Board erred for all the reasons

discussed above regarding the ‘118 claims.”).

Second, ABT argues, without factual support or citation to the

record, that the claims of the ‘256 application “do not refer to a ‘rather

large genus.’” Appellant Br. 54. ABT merely recites certain limitations

of the ‘256 claims without explaining the significance.

Beyond those two general contentions, ABT does not provide any

basis to conclude that there was no substantial evidence supporting the

Board’s decision. ABT does not address the evidence supporting the

Board’s decision. Dr. Phinney testified that, “[a]t most, Applicants of

the ‘256 application have allegedly provided evidence of a single

example, of a single, extremely rare cell population isolated from

human bone marrow (on average, one cell out of every 2-3 million cells

isolated from a bone marrow sample).” Appx2963; see also Appx245-

392. Dr. Phinney further explained that there was “[n]o actual isolation

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of any cell types from liver or brain, are provided in the ’256

application.” Appx2963; see also Appx245-392.

This evidence, together with the evidence detailed above,

constitutes substantial evidence supporting the Board’s factual

determination that the Furcht ‘256 application does not provide

adequate written description support for the broad claims.

VIII. The Board Correctly Held That No Interference-In-Fact Existed


Between Any Furcht Claim And Any Ho Claim

The Board held that there was no interference-in-fact. On appeal,

ABT’s challenge to the Board’s decision is based entirely on its

arguments presented in the context of the written description issues.

See Appellant Br. 55-58. For the above reasons, the Board’s decision

should be affirmed.

Further, ABT challenges the interference-in-fact ruling with

respect to only the Furcht ‘037 patent. ABT does not challenge the

Board’s decision that there is no interference-in-fact for its ‘118 patent

and ‘256 application.

A. Legal Standard

“An interference exists if the subject matter of a claim of one party

would, if prior art, have anticipated or rendered obvious the subject

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matter of a claim of the opposing party and vice versa.” 37 C.F.R.

§ 41.203(a); Eli Lilly v. Bd. of Regents of the Univ. of Wash., 334 F.3d

1264, 1267 (Fed. Cir. 2003). The Board applies the two-way test in

determining whether there is an interference-in-fact. Lilly, 334 F.3d at

1268. Here, the Board correctly held that no interference-in-fact existed

between any Furcht claim and any Ho claim.

In reviewing the Board’s application of the two-way test, this

Court “reviews, where necessary, both the subsidiary findings of

anticipation and/or obviousness as they relate to the application of the

test. See Medichem, S.A. v. Rolabo, S.L., 437 F3d 1157, 1164 (Fed. Cir.

2006) (citing Medichem, S.A. v. Rolabo, S.L., 353 F.3d 928, 932 (Fed.

Cir. 2003)).

B. ABT’s Argument is Entirely Based on the Same Arguments


Concerning Written Description

As noted above, ABT disputes the Board’s decision only on the

basis of the same reasons presented for challenging the Board’s decision

concerning written description. ABT recites those seven points on

pages 57-58 of its brief. Those seven factual disputes are fully

addressed above. ABT’s challenge should be rejected for the same

reasons set forth above.

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Further, Dr. Phinney provided detailed reasons supported by

evidence and testimony of why the claims of the Furcht ‘037 patent are

not anticipated or obvious in view of the Ho claims. Appx2420-2429.

ABT does not challenge that testimony on appeal.

IX. If The Court Remands, The Board Should Rule That The Furcht
Claims Are Not Enabled

During the interference proceeding, Ho sought judgment that the

Furcht claims are not enabled. Appx732-744; Appx2943-2958. While

the Board found many facts which establish the non-enablement of the

claims, the Board did not reach the issue of enablement. Appx45. If the

Court were to remand this case for any reason, the Board should be

instructed to rule on Ho’s motion that the Furcht claims are not enabled

under 35 U.S.C. § 112.

X. Conclusion

For the above reasons, the Board’s decision should be affirmed. In

the event the Board’s decision is not affirmed, the Board should be

instructed to address Ho’s motion that the Furcht claims are not

enabled under 35 U.S.C. § 112, and to decide the doubling rate,

inventorship, and inequitable conduct issues.

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Date: November 22, 2016 Respectfully submitted,

/s/ Matthew J. Dowd


Matthew J. Dowd
Dowd PLLC
1717 Pennsylvania Avenue, NW
Suite 1025
Washington, D.C. 20006
mjdowd@dowdpllc.com

Cynthia M. Bouchez
Medler Ferro Woodhouse & Mills
PLLC
8201 Greensboro Drive, Suite 1060
McLean, VA 22102
cbouchez@medlerferro.com

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CERTIFICATE OF COMPLIANCE

This brief complies with the word-length limitation of Federal

Rule of Appellate Procedure 28(e)(2)(A)(i). This brief contains

13,448 words, excluding the portions set forth in FRAP 32(a)(7)(B)(iii)

and Federal Circuit Rule 32(b). This brief complies with the typeface

requirements of Federal Rule of Appellate Procedure 32(a)(5) and the

type style requirements of Federal Rule of Appellate Procedure 32(a)(6).

The brief has been prepared in a proportionally spaced typeface using

Microsoft® Word and 14-point Century type.

/s/ Matthew J. Dowd


Matthew J. Dowd
Dowd PLLC
1717 Pennsylvania Avenue, NW
Suite 1025
Washington, D.C. 20006
mjdowd@dowdpllc.com

Dated: November 22, 2016


Case: 16-2116 Document: 25 Page: 85 Filed: 11/23/2016

CERTIFICATE OF SERVICE

I hereby certify that on this day, November 23, 2016, the foregoing
was electronically filed and therefore served electronically via the
court’s ECF/CM system on all counsel of record.

/s/ Matthew J. Dowd


Matthew J. Dowd
Dowd PLLC
1717 Pennsylvania Avenue, NW
Suite 1025
Washington, D.C. 20006
mjdowd@dowdpllc.com

Dated: November 23, 2016